Colonic sodium-potassium adenosine triphosphate subunit gene expression: ontogeny and regulation by adrenocortical steroids

Abstract

Mineralocorticoids and glucocorticoids exhibit overlapping but distinct effects on transepithelial sodium transport in the descending colon. Na,K-ATPase, the major sodium pump, has been variously reported to be regulated by one or both classes of steroids. The present studies explore the ontogeny and steroidal regulation of Na,K-ATPase alpha- and beta-subunit mRNA levels in the descending colon. In descending colon, subunit mRNA levels are low before birth, increasing to reach adult levels at approximately day 25. Dexamethasone treatment caused a rapid dose-dependent increase in colonic Na,K-ATPase subunit mRNA levels. The specific glucocorticoid RU26988 also increased subunit mRNA levels. Aldosterone administration, at doses adequate to yield a profound antinatriuresis, did not alter subunit mRNA levels. Carbenoloxone sodium produced an approximately 3-fold increase in subunit mRNA levels in intact but not adrenalectomized rats. We have demonstrated that Na,K-ATPase subunit gene expression is: 1) low in the fetal colon but achieves plateau levels by day 25; 2) acutely regulated by corticosteroids via type II rather than type I receptors; and 3) increased by carbenoxolone sodium, presumably as a result of increased occupancy of the type II receptor by corticosterone.